Febuxostat

Pronunciation

Pronunciation: feb-UX-oh-stat
Class: Xanthine oxidase inhibitor

Trade Names

Uloric
- Tablets 40 mg
- Tablets 80 mg

Pharmacology

Decreases serum uric acid by inhibiting xanthine oxidase.

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Pharmacokinetics

Absorption

At least 49% absorbed. T max is 1 to 1.5 h. C max is approximately 1.6 mcg/mL.

Distribution

Vd is 50 L. Plasma protein binding is approximately 99.2%, primarily to albumin.

Metabolism

Extensively metabolized by both conjugation via uridine diphosphate glucuronosyltransferase enzymes and oxidation via CYP enzymes, including CYP1A2, 2C8, and 2C9, as well as non-P450 isozymes.

Elimination

Mean terminal elimination half-life is approximately 5 to 8 h. Approximately 49% is recovered in the urine and approximately 45% is recovered in the feces.

Special Populations

Renal Function Impairment

Use with caution in patients with severe renal function impairment (CrCl 10 to 29 mL/min). Pharmacokinetics have not been studied in patients with end-stage renal function impairment who are on dialysis.

Hepatic Function Impairment

Studies have not been conducted in patients with severe hepatic function impairment; use with caution.

Gender

Following multiple oral doses, C max and AUC are 30% and 14% higher in women than men, respectively. However, no dosage adjustment is necessary.

Indications and Usage

Chronic management of hyperuricemia in patients with gout.

Contraindications

Coadministration with azathioprine, mercaptopurine, or theophylline.

Dosage and Administration

Adults

PO Start with 40 mg once daily. The dosage may be increased to 80 mg once daily for patients who do not achieve a serum uric acid less than 6 mg/dL after 14 days.

General Advice

  • May be taken without regard to meals or antacid use.

Storage/Stability

Store at 59° to 86°F. Protect from light.

Drug Interactions

Drugs metabolized by xanthine oxidase (eg, azathioprine, mercaptopurine, theophylline)

Plasma concentrations of these agents may be increased, leading to toxicity. Coadministration with febuxostat is contraindicated.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Dizziness (at least 1%).

Dermatologic

Rash (2%).

GI

Nausea (1%).

Hepatic

Abnormal LFTs (7%).

Musculoskeletal

Arthralgia (1%).

Precautions

Monitor

Monitor for signs and symptoms of MI and stroke. Assessment of liver function at 2 and 4 mo following the start of therapy and periodically thereafter is recommended.


Pregnancy

Category C .

Lactation

Undermined.

Children

Safety and efficacy not established.

Renal Function

Use with caution in patients with severe renal function impairment.

Hepatic Function

Use with caution in patients with severe hepatic function impairment.

CV events

Cardiovascular thromboembolic events may occur.

Hepatic enzymes

Transaminase elevations more the 3 times the ULN have been reported.

Gout flares

May occur after initiation of treatment because of changing serum uric acid levels resulting from mobilization of urate from tissue deposits. Flare prophylaxis with NSAIDs or colchicine is recommended upon starting treatment. It may not be necessary to discontinue therapy if a gout flare occurs during treatment. Manage gout flare, as appropriate for the individual patient.

Secondary hyperuricemia

Use is not recommended in patients with a greatly increased rate of urate formation (eg, malignant disease and its treatment).

Overdosage

Symptoms

Overdosage has not been reported.

Patient Information

  • Instruct patients to contact health care provider if they experience chest pain, rash, shortness of breath, or neurologic symptoms suggesting a stroke.
  • Advise patients that product may be taken without regard to meals.
  • Advise patient that concomitant prophylaxis with an NSAID or colchicine for gout flares may be used.

Copyright © 2009 Wolters Kluwer Health.

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